Hairy cell leukemia
Section editor | |
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Sanjai Sharma, MD Visalia, CA |
12 regimens on this page
17 variants on this page
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Guidelines
ESMO
- 2015: Robak et al. Hairy cell leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Hairy Cell Leukemia Foundation
- 2017: Grever et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia
NCCN
Untreated
Cladribine monotherapy
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Variant #1, 0.1 mg/kg/day x 7 days
Study | Evidence |
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Piro et al. 1990 | Pilot, <20 pts |
Tallman et al. 1996 | Phase II |
Chemotherapy
- Cladribine (Leustatin) 0.1 mg/kg/day IV continuous infusion on days 1 to 7 (total dose per cycle: 0.7 mg/kg)
7-day course
Variant #2, 0.12 mg/kg/day x 5 days
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robak et al. 1999 | Phase II | ||
Robak et al. 2007 | Phase III (C) | Weekly Cladribine | Seems not superior |
Chemotherapy
Cladribine (Leustatin) 0.12 mg/kg IV over 2 hours once per day for 5 consecutive days
One course
Variant #3, 0.14 mg/kg/day x 5 days
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zenhäusern et al. 2009 (SAKK 32/98) | Phase III (C) | Weekly Cladribine | Seems not superior |
Chemotherapy
- Cladribine (Leustatin) 0.14 mg/kg/day SQ bolus injection on days 1 to 5 (total dose per cycle: 0.7 mg/kg)
5-day course
Variant #4, 0.15 mg/kg/day x 5 days
Study | Evidence |
---|---|
Damasio et al. 1998 | Phase II |
Chemotherapy
Cladribine (Leustatin) 0.15 mg/kg IV over 2 hours once per day for 5 consecutive days
One course
References
- Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. 1990 Apr 19;322(16):1117-21. link to original article contains protocol PubMed
- Tallman MS, Hakimian D, Rademaker AW, Zanzig C, Wollins E, Rose E, Peterson LC. Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience. Blood. 1996 Sep 15;88(6):1954-9. link to original article contains verified protocol PubMed
- Update: Chadha P, Rademaker AW, Mendiratta P, Kim B, Evanchuk DM, Hakimian D, Peterson LC, Tallman MS. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood. 2005 Jul 1;106(1):241-6. Epub 2005 Mar 10. link to original article contains protocol PubMed content property of HemOnc.org
- Damasio EE, Resegotti L, Masoudi B, Bruni R, Cerri R, Isaza A, Clavio M, Risso M, Rossi E, Spriano M, Truini M. Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for the treatment of hairy cell leukemia: a study by Italian Group for the Hairy Cell Leukemia. Recenti Prog Med. 1998 Feb;89(2):68-73. PubMed
- Robak T, Błasińska-Morawiec M, Błoński J, Hellmann A, Hałaburda K, Konopka L, Kotlarek-Haus S, Potoczek S, Hansz J, Dmoszyńska A, Urasiński I, Zdziarska B, Dwilewicz-Trojaczek J, Hołowiecki J, Skotnicki AB. 2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland. Eur J Haematol. 1999 Jan;62(1):49-56. PubMed
- Robak T, Jamroziak K, Gora-Tybor J, Blonski JZ, Kasznicki M, Dwilewicz-Trojaczek J, Wiater E, Zdunczyk A, Dybowicz J, Dmoszynska A, Wojtaszko M, Zdziarska B, Calbecka M, Kostyra A, Hellmann A, Lewandowski K, Stella-Holowiecka B, Sulek K, Gawronski K, Skotnicki AB, Nowak W, Zawilska K, Molendowicz-Portala L, Kloczko J, Sokolowski J, Warzocha K, Seferynska I, Ceglarek B, Konopka L. Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial. Blood. 2007 May 1;109(9):3672-5. Epub 2007 Jan 5. link to original article contains verified protocol PubMed
- SAKK 32/98: Zenhäusern R, Schmitz SF, Solenthaler M, Heim D, Meyer-Monard S, Hess U, Leoncini L, Bargetzi M, Rufener B, Tobler A. Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98). Leuk Lymphoma. 2009 Sep;50(9):1501-11. link to original article contains verified protocol PubMed
Cladribine & Rituximab
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Regimen
Study | Evidence |
---|---|
Ravandi et al. 2011 | Phase II |
Chemotherapy, part 1
- Cladribine (Leustatin) 5.6 mg/m2 IV over 2 hours once per day on days 1 to 5
Supportive medications
All were administered at the discretion of the treating physician.
One course
28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started:
Chemotherapy, part 2
- Rituximab (Rituxan) 375 mg/m2 IV once per week for 8 weeks
One course
References
- Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. link to original article contains verified protocol link to PMC article PubMed
- Update: Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed
Pentostatin monotherapy
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Variant #1
Study | Evidence |
---|---|
Spiers et al. 1987 | Non-randomized |
Chemotherapy
- Pentostatin (Nipent) 5 mg/m2 IV over 2 minutes once per day on days 1 & 2
14-day cycles, continued to the point of maximal response or treatment failure
Variant #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Grever et al. 1995 | Phase III (E) | Interferon alfa-2a | Superior RFS |
Note: patients who had complete response before 6 months were given 2 additional cycles of pentostatin, and then treatment was stopped. Patients with objective partial response after 6 months of treatment received an additional 6 months of additional therapy, until they had a complete response or progression of disease.
Chemotherapy
- Pentostatin (Nipent) 4 mg/m2 IV rapid injection once on day 1
- Grever et al. 1995: Patients with performance status of 3 received an initial dose of 2 mg/m2 IV rapid injection once on day 1, which would be increased in later cycles to 4 mg/m2 IV rapid injection once on day 1 if patients had no adverse reactions.
- Grever et al. 1995: Doses of pentostatin were held for patients who had an increase in the serum creatinine concentration greater than 20% above their baseline. Pentostatin was not given until renal function returned to baseline or if 24-hour creatinine clearance was greater than 50 mL/min/1.73m2.
Supportive medications
- 1.5 liters of IV fluid hydration with every dose
14 day cycles (see note)
References
- Spiers AS, Moore D, Cassileth PA, Harrington DP, Cummings FJ, Neiman RS, Bennett JM, O'Connell MJ. Remissions in hairy-cell leukemia with pentostatin (2'-deoxycoformycin). N Engl J Med. 1987 Apr 2;316(14):825-30. link to original article contains verified protocol PubMed
- Update: Cassileth PA, Cheuvart B, Spiers AS, Harrington DP, Cummings FJ, Neiman RS, Bennett JM, O'Connell MJ. Pentostatin induces durable remissions in hairy cell leukemia. J Clin Oncol. 1991 Feb;9(2):243-6. link to original article contains protocol PubMed
- Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson BD. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol. 1995 Apr;13(4):974-82. link to original article contains verified protocol PubMed
- Update: Flinn IW, Kopecky KJ, Foucar MK, Head D, Bennett JM, Hutchison R, Corbett W, Cassileth P, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson B, Grever MR. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood. 2000 Nov 1;96(9):2981-6. link to original article contains verified protocol PubMed
Relapsed or refractory
BR
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BR: Bendamustine, Rituximab
Regimen
Study | Evidence |
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Burotto et al. 2013 | Pilot, <20 patients |
Note: this was a dose-escalation study and the bendamustine dose was selected for further study based on absence of DLT.
Chemotherapy
- Bendamustine 90 mg/m2 IV once per day on days 1 & 2
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1 & 15
28-day cycle for 6 cycles
References
- Burotto M, Stetler-Stevenson M, Arons E, Zhou H, Wilson W, Kreitman RJ. Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Clin Cancer Res. 2013 Nov 15;19(22):6313-21. Epub 2013 Oct 28. link to original article link to PMC article PubMed
Cladribine & Rituximab
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Regimen
Study | Evidence |
---|---|
Ravandi et al. 2011 | Phase II, <20 pts in this cohort |
Chemotherapy, part 1
- Cladribine (Leustatin) 5.6 mg/m2 IV over 2 hours once per day on days 1 to 5
Supportive medications
All were administered at the discretion of the treating physician.
One course
28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started:
Chemotherapy, part 2
- Rituximab (Rituxan) 375 mg/m2 IV once per week for 8 weeks
One course
References
- Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. link to original article contains verified protocol link to PMC article PubMed
- Update: Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed
Interferon alfa monotherapy
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Regimen
Study | Evidence |
---|---|
Quesada et al. 1984 | Pilot, <20 pts |
Golomb et al. 1986 | Non-randomized |
Of historic interest. Most patients had previously undergone splenectomy.
Immunotherapy
References
- Quesada JR, Reuben J, Manning JT, Hersh EM, Gutterman JU. Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med. 1984 Jan 5;310(1):15-8. link to original article PubMed
- Golomb HM, Jacobs A, Fefer A, Ozer H, Thompson J, Portlock C, Ratain M, Golde D, Vardiman J, Burke JS, Brady J, Bonnem E, Spiegel R. Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. J Clin Oncol. 1986 Jun;4(6):900-5. link to original article PubMed
Moxetumomab pasudotox monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence |
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Kreitman et al. 2012 (Study 1053) | Phase I |
Chemotherapy
- Moxetumomab pasudotox (Lumoxiti) 0.04 mg/kg IV over 30 minutes once per day on days 1, 3, 5
28-day cycle for up to 6 cycles
References
- Phase 1: Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, Fitzgerald DJ, Lechleider R, Pastan I. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1822-8. Epub 2012 Feb 21. link to original article link to PMC article PubMed
- Update: Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, FitzGerald DJ, Santiago L, Gao G, Lanasa MC, Pastan I. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood. 2018 May 24;131(21):2331-2334. Epub 2018 Feb 27. link to original article PubMed
Rituximab monotherapy
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Regimen
Study | Evidence |
---|---|
Nieva et al. 2003 | Phase II |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once per week for 4 consecutive weeks
- Initial infusions were given at 50 mg per hour for the first 30 minutes, and if no toxicity was observed, the infusion rate was escalated at 30-minute intervals to a peak infusion rate of 300 mg per hour.
Supportive medications
- Allopurinol (Zyloprim) 300 mg PO once per day for the first 7 days of treatment
One 4-week course
References
- Nieva J, Bethel K, Saven A. Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood. 2003 Aug 1;102(3):810-3. link to original article contains verified protocol PubMed
Vemurafenib monotherapy
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Tiacci et al. 2015 (MSKCC 12-200) | Phase II | ORR: 96-100% |
Note that a pooled analysis of two phase II trials is reported; they have slightly different durations - please see original text for details.
Chemotherapy
- Vemurafenib (Zelboraf) 960 mg PO twice per day
Up to 16 weeks (Italian trial) or 24 weeks (U.S. trial)
References
- MSKCC 12-200: Tiacci E, Park JH, De Carolis L, Chung SS, Broccoli A, Scott S, Zaja F, Devlin S, Pulsoni A, Chung YR, Cimminiello M, Kim E, Rossi D, Stone RM, Motta G, Saven A, Varettoni M, Altman JK, Anastasia A, Grever MR, Ambrosetti A, Rai KR, Fraticelli V, Lacouture ME, Carella AM, Levine RL, Leoni P, Rambaldi A, Falzetti F, Ascani S, Capponi M, Martelli MP, Park CY, Pileri SA, Rosen N, Foà R, Berger MF, Zinzani PL, Abdel-Wahab O, Falini B, Tallman MS. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med. 2015 Oct 29;373(18):1733-47. Epub 2015 Sep 9. link to original article contains verified protocol link to PMC article PubMed
Hairy cell leukemia variant (HCLv), all lines of therapy
Note: this is a distinct disease process from hairy cell leukemia, but will be included on this page for now given the similarities. We may create a dedicated page in the future.
Cladribine & Rituximab
back to top |
Regimen
Study | Evidence |
---|---|
Ravandi et al. 2011 | Phase II, <20 pts in this cohort |
Chemotherapy, part 1
- Cladribine (Leustatin) 5.6 mg/m2 IV over 2 hours once per day on days 1 to 5
Supportive medications
All were administered at the discretion of the treating physician.
One course
28 days after administration of cladribine, bone marrow examination was repeated, and then rituximab was started:
Chemotherapy, part 2
- Rituximab (Rituxan) 375 mg/m2 IV once per week for 8 weeks
One course
References
- Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011 Oct 6;118(14):3818-23. link to original article contains verified protocol link to PMC article PubMed
- Update: Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016 Sep;174(5):760-6. Epub 2016 Jun 15. link to original article link to PMC article PubMed